1. Field of the Invention
The present invention is broadly directed to methods of screening viral-binding compounds. In particular, the present invention provides cell-free assays to rapidly screen libraries of compounds for viral-capsid binding activity. Such compounds are useful for anti-viral treatments.
2. Description of Related Art
Picornaviruses represent a very large virus family of small ribonucleic acid-containing viruses responsible for many serious human and animal diseases (Rueckert, R. R. Virology, 2nd ed. (Field, B. N. et al., eds.) Raven Press, Ltd., New York, p. 508-548 (1982)). Picornaviruses include four major genera: enteroviruses, rhinoviruses, cardioviruses and aphthoviruses. The enterovirus genus includes polioviruses and Coxsackieviruses, echoviruses, and four numbered human enterovirus species.
Poliovirus is the etiologic agent of the disease poliomyelitis in humans. The human rhinoviruses consist of at least 100 serotypes and are the primary causative agents of the common cold. The Coxsackieviruses (24 group A serotypes, 6 group B serotypes), echoviruses (34 serotypes) and human enteroviruses (four serotypes), are associated with a wide range of human diseases including summer flus, diarrhea, meningitis, hepatitis, pneumonitis, myocarditis, pericarditis, and diabetes (Melnick, J. L. Virology, 2nd ed. (Fields, B. N. et al., eds.) Raven Press Ltd., New York p549-605). These infections occur sporadically in the general population, but are becoming more common among children in day care and their parents and siblings. In general, the available drugs have either failed to demonstrate sufficient prophylactic effect or are converted in the body into inactive metabolites.
The current drugs have all been derived from the same parent compound that was found through large-scale random screening of known chemicals for activity against the virus. Such screening procedure is a very expensive and time-consuming process. There is a need in the art to develop quick and efficient assays to screen for anti-viral compounds. In particular, there is a need in the art to establish cell-free assays for screening viral-binding compounds, e.g., picornaviral-binding compounds and libraries of such compounds.
It is an object of the invention to provide a method for screening viral-binding compounds.
This and other objects of the invention are provided by one or more of the embodiments provided below.
In one embodiment of the invention there is provided a method for screening viral-binding compounds which comprises the steps of incubating in vitro one or more compounds with a viral site, wherein binding of a compound to the viral site inhibits viral infection, separating a viral site-bound compound from an unbound compound, and detecting the viral site-bound compound. In a preferred embodiment, the viral site is contained within a viral capsid.
The present invention provides in vitro assays for rapid screening of anti-viral compounds, especially viral-binding compounds. Such compounds can be therapeutically effective in anti-viral treatments.